title: Rho kinase inhibitors stimulate the migration of human cultured osteoblastic cells by regulating actomyosin activity.
abstract: We investigated the effects of Rho-associated kinase (ROCK) on migration and cytoskeletal organization in primary human osteoblasts and Saos-2 human osteosarcoma cells. Both cell types were exposed to two different ROCK inhibitors, Y-27632 and HA-1077. In the improved motility assay used in the present study, Y-27632 and HA-1077 significantly increased the migration of both osteoblasts and osteosarcoma cells on plastic in a dose-dependent and reversible manner. Fluorescent images showed that cells of both types cultured with Y-27632 or HA-1077 exhibited a stellate appearance, with poor assembly of stress fibers and focal contacts. Western blotting showed that ROCK inhibitors reduced myosin light chain (MLC) phosphorylation within 5 min without affecting overall myosin light-chain protein levels. Inhibition of ROCK activity is thought to enhance the migration of human osteoblasts through reorganization of the actin cytoskeleton and regulation of myosin activity. ROCK inhibitors may be potentially useful as anabolic agents to enhance the biocompatibility of bone and joint prostheses.
authors.affiliation: Department of Anatomy and Embryology, Ehime University Graduate School of Medicine, Ehime, Japan.
authors.forename: Xuejiao
authors.initials: X
authors.lastname: Zhang
authors.forename: Cheng
authors.initials: C
authors.lastname: Li
authors.forename: Huiling
authors.initials: H
authors.lastname: Gao
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Nabeka
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Shimokawa
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Wakisaka
authors.forename: Seiji
authors.initials: S
authors.lastname: Matsuda
authors.forename: Naoto
authors.initials: N
authors.lastname: Kobayashi
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives / Q000494:pharmacology; D000205:Actomyosin / Q000378:metabolism*; D000577:Amides / Q000494:pharmacology; D002465:Cell Movement; D002478:Cells, Cultured; D022001:Focal Adhesions; D006801:Humans; D018994:Myosin Light Chains / Q000378:metabolism; D010006:Osteoblasts / Q000378:metabolism*; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology; D022502:Stress Fibers; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000577:Amides; D018994:Myosin Light Chains; D047428:Protein Kinase Inhibitors; D011725:Pyridines; C108830:Y 27632; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000205:Actomyosin; D054460:rho-Associated Kinases; C049347:fasudil